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Cell lineage-specific genome-wide DNA methylation analysis of patients with paediatric-onset systemic lupus

Kit San Yeung1, Tsz Leung Lee2, Mo Yin Mok3

  • 1a Department of Paediatrics and Adolescent Medicine, Li Ka Shing Faculty of Medicine , The University of Hong Kong , Hong Kong , China.

Epigenetics
|February 27, 2019
PubMed

Insights

Paediatric-onset systemic lupus erythematosus (SLE) shows a distinct DNA methylation signature in immune cells. This study reveals cell-specific epigenetic changes crucial for understanding childhood SLE.

Area of Science:

  • Immunology
  • Epigenetics
  • Paediatric Rheumatology

Background:

  • Paediatric-onset systemic lupus erythematosus (SLE) often has a more severe clinical course than adult-onset SLE.
  • Genome-wide DNA methylation (DNAm) data are lacking for paediatric-onset SLE.
  • Understanding epigenetic alterations in childhood SLE is crucial for targeted therapies.

Purpose of the Study:

  • To investigate genome-wide DNA methylation patterns in paediatric-onset SLE.
  • To compare DNAm profiles across multiple immune cell lineages and whole blood.
  • To identify a disease-specific DNAm signature for childhood SLE.

Main Methods:

  • Genome-wide DNAm profiling using Illumina HumanMethylationEPIC BeadChip.
  • Analysis of purified immune cell lineages (CD4+ T cells, CD8+ T cells, B cells, neutrophils) and whole blood.
  • Comparison between 16 Chinese paediatric-SLE patients and 13 healthy controls.

Main Results:

  • A consistent DNAm signature characterized by hypomethylation at 21 CpG sites (15 genes) was identified in paediatric-SLE.
  • Cell lineage-specific DNAm changes (both hypomethylation and hypermethylation) were observed.
  • Epigenetic alterations involved both novel genes and those previously implicated in SLE pathogenesis.

Conclusions:

  • Paediatric-onset SLE exhibits a unique, cell-type-specific DNA methylation profile.
  • Studying DNAm in individual immune cell lineages provides deeper insights into SLE pathophysiology than whole blood analysis.
  • These findings may pave the way for novel diagnostic and therapeutic strategies for childhood SLE.

Keywords:
DNA methylationMethylationEPICSLEbloodcell compositioncell lineage-specificlupuspaediatric-onset

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